The DPP, nationally, recruited 3,234 volunteers who received standard lifestyle recommendations and were randomly assigned to one of three interventions: intensive lifestyle with the aim of losing and maintaining 7% weight loss and achieving > 150 minutes per week of moderate intensity physical activity, metformin therapy with 850 mg twice per day, or placebo. The development of diabetes in the lifestyle intervention and metformin-treated groups were reduced by 58% and 31%, respectively, compared with the placebo group Many important issues remained unanswered, however. Specifically, whether the decrease in the development of diabetes can be sustained is unknown. Moreover, determining whether the delay or prevention of diabetes will translate into a decrease in retinopathy, nephropathy, neuropathy, and cardiovascular disease, all of which require more years to develop than the DPP period of study, is critical to establish the true impact of the DPP on public health. This long-term follow-up study of the DPP the DPPOS will address these issues. All DPP participants, whether or not they developed diabetes during the DPP, were invited to join DPPOS. 91% of the participants in the American Indian centers chose to continue in DPPOS. This was the highest percentage of any racial/ethnic group in the DPPOS. The DPPOS has continued to progress very smoothly at the American Indian sites operated by the Diabetes Epidemiology and Clinical Research Section. Retention of American Indian participants is excellent. 94% of our participants are still actively followed (defined as not having missed the last two visits), compared with 91% in the study nationally. This allows Southwestern American Indians, a population highly affected by diabetes, to participant in this major clinical trial determining long-term health benefits of diabetes prevention interventions. Over 10 years, women with a history of GDM assigned to placebo had a 48% higher risk of developing diabetes compared with women without a history of GDM. In women with a history of GDM, ILS and metformin reduced progression to diabetes compared with placebo by 35% and 40%, respectively. Among women without a history of GDM, ILS reduced the progression to diabetes by 30%, and metformin did not reduce the progression to diabetes. During a mean follow-up of 15 years, diabetes incidence was reduced by 27% in the lifestyle intervention group and by 18% in the metformin group, compared with the placebo group, with declining between-group differences over time. The prevalences at the end of the study of the aggregate microvascular outcome were not significantly different between the treatment groups in the total cohort. However, in women the lifestyle intervention was associated with a lower prevalence than in the placebo and metformin groups, with reductions in the lifestyle intervention group of 21% (p=003) compared with placebo and 22% (p=002) compared with metformin. Compared with participants who developed diabetes, those who did not develop diabetes had a 28% lower prevalence of microvascular complications.